Selection criteria: &nbsp;Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes.

Review methods: &nbsp;Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol(5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals.

Results: &nbsp;53 prospective cohort studies with 1&thinsp;611&thinsp;339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality.

Conclusions: &nbsp;Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol.

Mentions:
Twenty four studies reported data for the association between prediabetes and risk of coronary heart disease. Similar to results for composite cardiovascular events, prediabetes was associated with increased risk of coronary heart disease when it was defined as IFG-ADA (relative risk 1.10, 95% confidence interval 1.04 to 1.16), IFG-WHO (1.18, 1.08 to 1.28), impaired glucose tolerance (1.20, 1.0 to 1.44), HbA1c 39-47 mmol/mol (1.15, 1.01 to 1.33), or HbA1c 42-47 mmol/mol (1.28, 1.03 to 1.59) (fig 4). Combined data from two studies, however, did not show an increased risk of coronary heart disease in people with both IFG-ADA and impaired glucose tolerance (0.93, 0.70 to 1.25). No studies reported the risk of coronary heart disease in people with both IFG-WHO and impaired glucose tolerance. There was no significant different in risk of coronary heart disease with different definition of prediabetes (P=0.36).

Mentions:
Twenty four studies reported data for the association between prediabetes and risk of coronary heart disease. Similar to results for composite cardiovascular events, prediabetes was associated with increased risk of coronary heart disease when it was defined as IFG-ADA (relative risk 1.10, 95% confidence interval 1.04 to 1.16), IFG-WHO (1.18, 1.08 to 1.28), impaired glucose tolerance (1.20, 1.0 to 1.44), HbA1c 39-47 mmol/mol (1.15, 1.01 to 1.33), or HbA1c 42-47 mmol/mol (1.28, 1.03 to 1.59) (fig 4). Combined data from two studies, however, did not show an increased risk of coronary heart disease in people with both IFG-ADA and impaired glucose tolerance (0.93, 0.70 to 1.25). No studies reported the risk of coronary heart disease in people with both IFG-WHO and impaired glucose tolerance. There was no significant different in risk of coronary heart disease with different definition of prediabetes (P=0.36).

Selection criteria: &nbsp;Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes.

Review methods: &nbsp;Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol(5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals.

Results: &nbsp;53 prospective cohort studies with 1&thinsp;611&thinsp;339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality.

Conclusions: &nbsp;Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol.